| Aerosols for sinunasal drug delivery -> Monitor Keywords |
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Aerosols for sinunasal drug deliveryRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Effervescent Or Pressurized Fluid Containing, Organic Pressurized FluidAerosols for sinunasal drug delivery description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070202051, Aerosols for sinunasal drug delivery. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] The present invention is related to pharmaceutical aerosols and to liquid compositions which are suitable for aerosolisation. In further aspects, the invention relates to therapeutic uses of aerosols and to methods of producing them and of administering them to patients. The aerosols are suitable for delivering drug substances to selected regions within the respiratory tract, including the nasal cavity and the paranasal sinuses. BACKGROUND OF THE INVENTION [0002] Diseases and conditions affecting either paranasal sinuses or both the nasal cavity and the paranasal sinuses, in particular acute and chronic forms of rhinosinusitis, are increasing in incidence and prevalence in many countries and regions of the world, including Europe and the United States. These conditions may be associated with significant symptoms and have a negative impact on quality of life and daily functioning. [0003] On the other hand, the effective treatment of the nasal and paranasal mucosa remains challenging. While the mucosa of the nasal cavity is a feasible target for locally administered drugs formulated as nasal sprays, the sinuses are not easily accessed by liquid formulations. In the case of relatively coarse aerosols, such as conventional nasal sprays, the deposition on the sinus mucosa is negligible, and even finer aerosols, such as those generated by nebulisers, exhibit a very low degree of sinus deposition. [0004] The primary reason for the lack of access of an inhaled aerosol to the sinuses is anatomical: in contrast to the nasal cavity, the sinuses are not actively ventilated. They are connected to the nasal passage via small orifices called ostia, whose diameter is typically in the region of only about 0.5 to 2 mm. When air is inhaled through the nose and passes through the nasal passage into the trachea, there is only very little convective flow into the ostia. [0005] To address the need for devices and methods which are more effective in delivering an aerosol to the paranasal sinuses, it was suggested in WO 2005/023335 that certain particle size and velocity characteristics must be achieved in order that a majority of an aerosolised drug formulation reaches the deep nasal cavities and the sinuses. [0006] Furthermore, WO 2004/020029 discloses an aerosol generator comprising a nebuliser and a compressor which delivers a vibrating stream of air to the nebuliser. The document further describes that the aerosol emitted from the nebuliser should be inhaled through one nostril via an appropriate nosepiece, and that the other nostril should be closed by an appropriate device. [0007] However, it has been found by the inventors that these teachings of the prior art do not actually ensure the deposition of a large fraction on the sinunasal mucosa, depending on the actual configuration of the devices and the aerosol characteristics. Thus, there remains a need for further improvements with regard to the aerosol generators and the aerosol formulations in order to allow an improved therapy of sinunasal diseases and conditions. [0008] It is therefore an object of the present invention to provide improved pharmaceutical aerosols which are useful for delivering active compounds to the mucosa of the paranasal sinuses or of both the nasal cavity and the paranasal sinuses. Furthermore, it is an object of the invention to provide methods for producing such aerosols. Further objects will become clear on the basis of the following desciption and the patent claims. SUMMARY OF THE INVENTION [0009] In a first principal aspect, the invention provides an aerosol for delivering an active compound to the mucosa of the nose or of a paranasal sinus. The aerosol comprises a dispersed liquid phase and a continuous gas phase. The volume of the dispersed liquid phase which contains a unit dose of the active compound is less than about 5 mL. The mass median diameter of the dispersed liquid phase is from about 2.0 to about 6.0 .mu.m. Furthermore, the pressure of the aerosol pulsates with a frequency in the range from about 10 to about 90 Hz. [0010] In a second principal aspect, the invention provides a method for producing a pharmaceutical aerosol for the delivery of an active compound to the mucosa of the nose or of a paranasal sinus. Again, the aerosol comprises a dispersed liquid phase and a continuous gas phase. The method involves the steps of (a) providing an aerosol generator capable of emitting an aerosol whose pressure pulsates with a frequency in the range from about 10 to about 90 Hz, wherein the aerosol generator is adapted to maintain an amplitude of pressure pulsation of the emitted aerosol of at least about 10 mbar, (b) providing a liquid composition comprising said active compound, wherein a unit dose of the active compound is comprised in a volume of less than about 5 mL of said liquid composition, and (c) aerosolising said liquid composition. [0011] The method is preferably practised with an aerosol generator which is capable not only of delivering an aerosol which pulsates at the specified frequency, but which is also capable to maintain an amplitude of pressure pulsation of at least about 10 mbar. The aerosol generator comprises a nebuliser which may, for example, be an electronic vibrating membrane nebuliser or a jet nebuliser connected to a suitable air compressor. [0012] The active compound may be selected from various therapeutic categories, such as from anti-inflammatory compounds, glucocorticoids, anti-infective agents, antibiotics, antifungals, antivirals, mucolytics, antiseptics, wound healing agents, local anaesthetics, peptides, and proteins. [0013] The method of the invention, and the aerosols thus produced, achieve a high deposition of drug in the nasal cavities and/or paranasal sinuses. Thus, they are preferably used for the prevention, management, or treatment of a disease, symptom, or condition selected from acute and chronic sinusitis, such as allergic sinusitis, seasonal sinusitis, bacterial sinusitis, fungal sinusitis, viral sinusitis, frontal sinusitis, maxillary sinusitis, sphenoid sinusitis, ethmoid sinusitis, vacuum sinusitis; acute and chronic rhinitis, such as allergic rhinitis, seasonal rhinitis, bacterial rhinitis, fungal rhinitis, viral rhinitis, atrophic rhinitis, vasomotor rhinitis; any combination of rhinitis and sinusitis (i.e. rhinosinusitis); nasal polyps, nasal furuncles, epistaxis, wounds of the nasal or sinunasal mucosa, such as after injury or surgery; and dry nose syndrome. [0014] In further embodiments, the active compound is poorly water-soluble, and formulated with the use of particular formulation techniques in order that the volume of liquid which contains a unit dose is not more than about 5 mL, and that the duration of aerosol generation and administration is still convenient to the patients. Such formulation techniques include drug nanoparticles, colloidal carrier systems, or the use of solubility-enhancing agents. Preferably, the duration of administration is not more than about 30 minutes, or not more than about 20 minutes according to another embodiment. [0015] Further embodiments of the invention will become obvious on the basis of the following detailed description, the examples and the patent claims. DETAILED DESCRIPTION OF THE INVENTION [0016] In a first aspect, the invention provides a pharmaceutical aerosol for the delivery of an active compound to the mucosa of the nose or of a paranasal sinus comprising a dispersed liquid phase and a continuous gas phase. The volume of the dispersed liquid phase comprising a unit dose of the active compound is less than about 5 mL. The mass median diameter of the dispersed liquid phase is from about 2.0 to about 6.0 .mu.m, as measured by laser diffraction. Furthermore, the pressure of the aerosol pulsates with a frequency in the range from about 10 to about 90 Hz. [0017] In a second principal aspect, the invention provides a method for producing a pharmaceutical aerosol for the delivery of an active compound to the mucosa of the nose or of a paranasal sinus, said aerosol comprising a dispersed liquid phase and a continuous gas phase. The method comprises the steps of (a) providing an aerosol generator capable of emitting an aerosol whose pressure pulsates with a frequency in the range from about 10 to about 90 Hz, wherein the aerosol generator is adapted to maintain an amplitude of pressure pulsation of the emitted aerosol of at least about 10 mbar, (b) providing a liquid composition comprising said active compound, wherein a unit dose of the active compound is comprised in a volume of less than about 5 mL of said liquid composition, and (c) aerosolising said liquid composition. [0018] As used herein, an aerosol is a dispersion of a solid or liquid phase in a gas phase. The dispersed phase, also termed the discontinuous phase, is comprised of multiple solid or liquid particles. Typically, the particle size of the dispersed phase is less than about 100 .mu.m, and considerably less than that. Both basic physical types of aerosols, i.e. solid and liquid dispersions in a gas phase, may be used as pharmaceutical aerosols. Examples of aerosols representing solid particles in a gas phase or those emitted by dry powder inhalers (DPI's). In contrast, pressurised metered-dose inhalers and nebulisers deliver aerosols whose dispersed phase is liquid. [0019] According to the present invention, the aerosol comprises a dispersed liquid phase and a continuous gas phase. Such aerosols are sometimes referred to as "liquid aerosols" or, probably more appropriately, aerosolised liquids. It should be noted that the requirement of a dispersed liquid phase does not exclude the presence of a solid phase. In particular, the dispersed liquid phase may itself represent a dispersion, such as a suspension of solid particles in a liquid. [0020] The continuous gas phase may be selected from any gas or mixture of gases which is pharmaceutically acceptable. For example, the gas phase may simply be air or compressed air, which is most common in inhalation therapy using nebulisers as aerosol generators. Alternatively, other gases and gas mixtures, such as air enriched with oxygen, or mixtures of nitrogen and oxygen may be used. Most preferred is the use of air as continuous gas phase. Continue reading about Aerosols for sinunasal drug delivery... Full patent description for Aerosols for sinunasal drug delivery Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Aerosols for sinunasal drug delivery patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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